Clinical Trials Register

Summary
EudraCT Number:	2013-002899-41
Sponsor's Protocol Code Number:	8-55-52966-005
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-01-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2013-002899-41

A.3

Full title of the trial

A dose escalation, proof of concept, phase IIa study to investigate the safety and tolerability, the pharmacokinetic and the
pharmacodynamic of BN82451B, administered twice daily over 4 weeks, in male patients with Huntington’s disease

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study to assess the effects of BN82451B and how it is absorbed, distributed and eliminated in the body, when it is given for 4 weeks to men suffering from Hungtington's disease

A.4.1

Sponsor's protocol code number

8-55-52966-005

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Ipsen Pharma
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ipsen Pharma
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ipsen Pharma
B.5.2	Functional name of contact point	Executive VP Research & Development
B.5.3	Address:
B.5.3.1	Street Address	65 quai Georges Gorse
B.5.3.2	Town/ city	Boulogne Billancourt
B.5.3.3	Post code	92100
B.5.3.4	Country	France
B.5.4	Telephone number	+33158335000
B.5.5	Fax number	+33158335001
B.5.6	E-mail	ct-application@ipsen.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BN8251B
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	918656-59-4
D.3.9.2	Current sponsor code	BN82451B
D.3.9.3	Other descriptive name	BN82451B
D.3.9.4	EV Substance Code	SUB33926
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BN8251B
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	918656-59-4
D.3.9.2	Current sponsor code	BN82451B
D.3.9.3	Other descriptive name	BN82451B
D.3.9.4	EV Substance Code	SUB33926
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Huntington's disease

E.1.1.1

Medical condition in easily understood language

Neurodegenerative genetic disorder

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10070668
E.1.2	Term	Huntington's disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of BN82451B versus placebo after oral administration twice daily (bid) for 28 days in subjects with Huntington’s Disease (HD).

E.2.2

Secondary objectives of the trial

• To characterise the pharmacokinetics (PK) of BN82451B and its metabolites (BN2468 and BN7167) in subjects with HD.
• To evaluate the effect of BN82451B compared with placebo, on quantitative measures of motor function (Q-Motor).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) Male subjects ≥ 20 to ≤ 70 years old.
(2) Provision of written informed consent prior to any study related procedures.
(3) Confirmed symptomatic HD diagnosed based on clinical features (i.e. Diagnostic Confidence Level = 4) and presence
of ≥ 36 CAG repeats in the Huntington gene as documented by a copy of a previous genetic test report.
(4) UDHRS-TMS ≥ 15.
(5) Ambulatory.
(6) UHDRS-Total Functional Capacity (TFC) ≥3 (i.e. Shoulson & Fahn Scale stages 1-3 inclusive)
(7) Subjects on antipsychotic, antidepressant, anxiolytic and hypnotic therapy must have been on stable treatment
4 weeks prior to study drug start and during the study period.
(8) Able to swallow study medication.
(9) Able to perform Q-Motor tests.
(10) If his partner is at risk of pregnancy, the subject agrees to use a condom or be abstinent for 14 days after the last intake of study drug.

E.4

Principal exclusion criteria

(1) Juvenile forms of HD.
(2) Any form of chorea other than HD.
(3) History of seizure, epilepsy or other convulsive disorder.
(4) History of conditions susceptible to induce seizures such as severe traumatic brain injury, brain tumours, stroke.
(5) History of neurosurgical procedure.
(6) Current evidence or history (within 1 year of Baseline) of psychosis, hallucinations or delusions, including major
depression with psychotic features, as defined in the Diagnostic and Statistical Manual, Fourth Edition, Text
Revision (DSM-IV-TR). Patients currently experiencing mild depression, or moderate depression which is adequately
and appropriately treated in the judgement of the investigator, can participate if depression is not expected to
interfere with study participation.
(7) History of drug and/or alcohol abuse as per the DSM IV-TR criteria within 12 months prior to Baseline.
(8) At imminent risk of self harm based on investigator’s clinical judgment, with a “yes” answer on item 4 or 5 on the
CSSRS questionnaire.
(9) Mini Mental State Exam (MMSE) total score ≤ 23.
(10) Used any investigational drugs within 30 days prior to Screening or 5 half lives, whichever is the longest.
(11) Known allergy/sensitivity to the study drugs or their excipients.
(12) A severe or ongoing unstable medical condition (e.g. cardiac, hepatic, renal, metabolic or endocrine).
(13) Any clinically significant condition which, in the opinion of the investigator, would interfere with the trial evaluations or
optimal participation in the trial.
(14) Any significant laboratory results which, in the investigator’s opinion, would not be compatible with study
participation or represent a risk for subjects while in the study.
(15) History of malignant disease within the 5 years prior to Screening (with the exception of basal cell and squamous
cell carcinomas of the skin that have been completely excised, in situ prostate cancer with a normal prostate
specific antigen).
(16) An estimated Creatinine Clearance (CrCl) of <60 mL/minute (using the Cockcroft-Gault formula).
(17) ALT or AST values ≥2x the Upper Limit of Normal range (ULN) or both or both GGT and ALP >3x ULN
(18) Known history of hepatitis B or C or Human Immunodeficiency Virus (HIV) or positive serology at
Screening.
(19) Corrected QT interval using Bazett's correction (QTcB) >450 ms or other clinically significant ECG findings.
(20) Receiving tetrabenazine within 4 weeks prior to Baseline
(21) Receiving drugs at doses known to induce seizures with an incidence of more than 1% as per the reference list
(22) Taking the following prohibited medications/substances: Strong Cytochrome (CYP) 3A4 inhibitors, strong CYP3A4 inducers and CYP2B6 substrates (Wash out prior to Baseline 30 days or 5 half lives,whichever is the longest). CYP1A2 substrates, CYP3A4 substrates and CYP2C19 substrates may be allowed and will be assessed on a case by case basis according to the dose received.

E.5 End points

E.5.1

Primary end point(s)

• Treatment emergent adverse events (TEAEs)
• Physical examination
• Neurological examination
• Vital signs (heart rate, systolic and diastolic blood pressure)
• 12-lead ECG
• CSSRS
• Biochemistry, haematology and urinalysis
• Platelet function

E.5.1.1

Timepoint(s) of evaluation of this end point

• Treatment emergent adverse events (TEAEs)
• Physical examination at Screening, Day -2, and EOS/early withdrawal
• Neurological examination at Screening and Days -2, 7, 14, 21, 28, 30 and EOS/early withdrawal
• Vital signs (heart rate, systolic and diastolic blood pressure) at Screening and Days -2, 1, 3, 7, 14, 21, 28, 30 and EOS/early
withdrawal
• 12-lead ECG at Screening and Days -2, 1, 3, 7, 14, 21, 28, 30 and EOS/early withdrawal
• CSSRS at Screening and Days -2, 7, 14, 21, 28 and EOS/early withdrawal
• Biochemistry, haematology and urinalysis at Screening and on Days -1, 7, 13, 21, 28 and 30 and EOS/early withdrawal
• Platelet function at Days -2, 13, 28 and EOS/early withdrawal

E.5.2

Secondary end point(s)

- Full PK assessments

-Q Motor test:
• Choreomotography (position index and orientation index of
grasp lift task)
• Manumotography (grip force variability of grasp lift task)
• Digitomotography (tap variability in index finger speeded
tapping task)
• Dysdiadochomotography (tap variability in alternating
pronation/supination hand tapping task)
• Pedomotography (tap variability in foot speeded tapping task)

E.5.2.1

Timepoint(s) of evaluation of this end point

Pharmacokinetic Evaluations:
• Full PK assessments will be performed on Days 1, 14 and 28 after the morning dose.
• After the morning dose on Days 7 and 21, 3 blood samples will be collected up to 12 hours post dose.
• Pre morning dose concentration will be performed on Days 12, 13, 26 and 27.
• Twelve hour urinalysis for PK assessments will be carried out on Days 1, 13 and 27.

Q-Motor tests will be assessed at Screening (training), Day -2, -1, 1, 4, 7, 10, 13, 14, 17, 20, 21, 24, 27, 28, 30 and EOS/early withdrawal.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

sequential cohorts

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

expected normal treatment of the condition

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-03-31

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